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Overexpression of circular RNA circ_001569 indicates poor prognosis in hepatocellular carcinoma and promotes cell growth and metastasis by sponging miR-411-5p and miR-432-5p

Liu, Hongyuan, Xue, Li, Song, Changyue, Liu, Fang, Jiang, Tingjun, Yang, Xiuhua
Biochemical and biophysical research communications 2018 v.503 no.4 pp. 2659-2665
RNA, animals, bioinformatics, carcinogenesis, cell growth, gain-of-function mutation, gene overexpression, hepatoma, loss-of-function mutation, luciferase, lungs, metastasis, patients, prognosis, quantitative polymerase chain reaction, reverse transcriptase polymerase chain reaction, therapeutics
Emerging evidence indicated that abnormally expressed circular RNAs (circRNAs) are critically involved in tumorigenesis and development of several cancers. However, the study relevant to the relationship between circRNAs and hepatocellular carcinoma (HCC) is rare. In this study, the expression of circ_001569 in HCC tissue specimens and cells were determined by qRT-PCR. The clinical relevance of circ_001569 was also analyzed. In addition, loss-of-function and gain-of-function assays were conducted to explore the biological functions of circ_001569. Furthermore, tumor formation and lung metastasis studies were induced to confirm the in vitro data. Mechanistically, bioinformatics analysis and luciferase reporter assays were conducted to illustrate the underlying mechanism of circ_001569. The results indicated that circ_001569 was overexpressed in HCC tissue samples and cells. This overexpression is correlated with larger tumor size, advanced TNM stages and unfavorable prognosis in the patients with HCC. Additionally, circ_001569 significantly facilitated HCC cell growth, migration and invasion. The animal studies further confirmed thein vitroresults. More importantly, circ_001569 could directly sponge miR-411-5p and miR-432-5p. The oncogenic functions of circ_001569 is partially dependent on its regulation on miR-411-5p and miR-432-5p. In summary, circ_001569/miR-411-5p/miR-432-5p regulatory signaling might be a rational HCC-related therapeutic target.